The identification of small organic molecules that affect specific biological functions is an endeavor that impacts both biology and medicine. Such molecules are useful as therapeutic agents and as probes of biological function. In but one example from the emerging field of chemical genetics, in which small molecules are used to alter the function of biological molecules to which they bind, small molecules have helped elucidate signal transduction pathways by acting as chemical protein knockouts. (Schreiber et al., J. Am. Chem. Soc., 1990, 112, 5583; Mitchison, Chem. and Biol., 1994, 1, 3). Of course, small molecules that interact with particular biological targets and affect specific biological functions, may also serve as candidates for the development of therapeutics. One important class of small molecules are natural products, which are small molecules obtained from nature. Natural products have played an important role in the development of biology and medicine, serving as pharmaceutical leads, drugs (Newman et al., Nat. Prod. Rep. 2000, 17, 215–234), and powerful reagents for studying cell biology (Schreiber, S. L. Chem. and Eng. News 1992 (October 26), 22–32). More generally, any organic compounds, whether naturally-occurring, reminiscent of natural products or artificially created (e.g., via chemical synthesis or semi-synthesis), are also of interest since they may serve as candidates for the development of therapeutics.
Because it is difficult to predict which small molecules will interact with a biological target, and it is often difficult to obtain or efficently synthesize small molecules found in nature, intense efforts have been directed toward the generation of large numbers, or libraries, of small organic compounds, often “natural product-like” libraries. These libraries can be tested in sensitive assays for a particular biological activity, such as binding to a target of interest.
Clearly, it would be desirable to develop compounds with a desired biological activity. Additionally, it would be desirable to identify novel compounds capable of acting as probes of biological function.